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  1. Saharudin S, Sanusi SY, Ponnuraj KT
    Clin Oral Investig, 2022 Feb;26(2):1261-1268.
    PMID: 34453594 DOI: 10.1007/s00784-021-04098-x
    OBJECTIVE: The aim of this study is to do a sequencing analysis of RUNX2 in non-syndromic patients with supernumerary tooth.

    MATERIALS AND METHODS: Fifty-three patients with supernumerary tooth were identified retrospectively from 1,275 radiographic reviews who attended the Hospital Universiti Sains Malaysia (USM) Dental Clinic. Informed consent was obtained from the patients prior to the study. Blood samples were collected from 41 patients and DNA extractions were performed out of which 10 samples were chosen randomly for PCR amplification using designated primers for RUNX2 followed by DNA sequencing analysis.

    RESULTS: This study involved 28 male patients (68.3%) and 13 female patients (31.7%) with a gender ratio of 2.2:1 and mean age of 15.9 ± 6.2 years. DNA extraction yielded ~ 40 ng/μl of concentrated DNA, and each DNA sample had more than 1500 bp of DNA length. The purity ranged between 1.8 and 2.0. DNA sequencing analysis did not reveal any mutations in exons 5 and 6 of RUNX2.

    CONCLUSION: This study did not reveal any mutations in exons 5 and 6 of RUNX2 in non-syndromic patients with supernumerary tooth.

    CLINICAL RELEVANCE: Analysis of mutations in RUNX2 is important to enhance the understanding of tooth development in humans.

    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/genetics
  2. Aisha MD, Nor-Ashikin MN, Sharaniza AB, Nawawi HM, Kapitonova MY, Froemming GR
    Exp Cell Res, 2014 Aug 1;326(1):46-56.
    PMID: 24928274 DOI: 10.1016/j.yexcr.2014.06.003
    Exposure of Normal Human Osteoblast cells (NHOst) to a period of hypothermia may interrupt their cellular functions, lead to changes in bone matrix and disrupt the balance between bone formation and resorption, resulting in bone loss or delayed fracture healing. To investigate this possibility, we exposed NHOst cells to moderate (35 °C) and severe (27 °C) hypothermia for 1, 12, 24 and 72 h. The effects of hypothermia with respect to cell cytoskeleton organization, metabolic activity and the expression of cold shock chaperone proteins, osteoblast transcription factors and functional markers, were examined. Our findings showed that prolonged moderate hypothermia retained the polymerization of the cytoskeletal components. NHOst cell metabolism was affected differently according to hypothermia severity. The osteoblast transcription factors Runx2 and osterix were necessary for the transcription and translation of bone matrix proteins, where alkaline phosphatase (Alp) activity and osteocalcin (OCN) bone protein were over expressed under hypothermic conditions. Consequently, bone mineralization was stimulated after exposure to moderate hypothermia for 1 week, indicating bone function was not impaired. The cold shock chaperone protein Rbm3 was significantly upregulated (p<0.001) during the cellular stress adaption under hypothermic conditions. We suggest that Rbm3 has a dual function: one as a chaperone protein that stabilizes mRNA transcripts and a second one in enhancing the transcription of Alp and Ocn genes. Our studies demonstrated that hypothermia permitted the in vitro maturation of NHOst cells probably through an osterix-dependent pathway. For that reason, we suggest that moderate hypothermia can be clinically applied to counteract heat production at the fracture site that delays fracture healing.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/genetics; Core Binding Factor Alpha 1 Subunit/metabolism*
  3. Puvaneswary S, Raghavendran HB, Talebian S, Murali MR, A Mahmod S, Singh S, et al.
    Sci Rep, 2016;6:24202.
    PMID: 27068453 DOI: 10.1038/srep24202
    In our previous study, we reported the fabrication and characterization of a novel tricalcium phosphate-fucoidan-chitosan (TCP-Fu-Ch) biocomposite scaffold. However, the previous report did not show whether the biocomposite scaffold can exhibit osteogenic differentiation of human bone marrow stromal cells in osteogenic media and normal media supplemented with platelet-derived growth factor (PDGF-BB). On day 15, the release of osteocalcin, was significant in the TCP-Fu-Ch scaffold, when compared with that in the TCP-Ch scaffold, and the level of release was approximately 8 and 6 ng/ml in osteogenic and normal media supplemented with PDGF-BB, respectively. Scanning electron microscopy of the TCP-Fu-Ch scaffold demonstrated mineralization and apatite layer formation on day 14, while the addition of PDGF-BB also improved the osteogenic differentiation of the scaffold. An array of gene expression analysis demonstrated that TCP-Fu-Ch scaffold cultured in osteogenic and normal media supplemented with PDGF-BB showed significant improvement in the expression of collagen 1, Runt-related transcription factor 2, osteonectin, bone gamma-carboxyglutamate protein, alkaline phosphatase, and PPA2, but a decline in the expression of integrin. Altogether, the present study demonstrated that fucoidan-incorporated TCP-Ch scaffold could be used in the differentiation of bone marrow stromal cells and can be a potential candidate for the treatment of bone-related ailments through tissue engineering technology.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit
  4. Khairani Idah Mokhtar, Noraini Abu Bakar, Azrul Fazwan Kharuddin
    MyJurnal
    Runt-related transcription factor 2 (RUNX2) plays important roles in osteoblast
    differentiation, tooth development and chondrocyte maturation; hence its involvement in
    craniofacial development is paramount. Mutation in RUNX2 is implicated with cleidocranial
    dysplasia; a bone development disorder, while single nucleotide polymorphism (SNP) in RUNX2 is
    associated with Class II/2 malocclusion. This study aimed to determine RUNX2 SNP of DNA marker
    (rs6930053) in malocclusion patients from local population. (Copied from article).
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit
  5. Abukhadir SS, Mohamed N, Makpol S, Muhammad N
    PMID: 23049610 DOI: 10.1155/2012/656025
    The study determines the effects of palm vitamin E on the gene expression of bone-formation-related genes in nicotine-treated rats. Male rats were divided into three groups: normal saline olive oil (NSO), nicotine olive oil (NO), and nicotine palm vitamin E (NE). The treatment was carried out in 2 phases. During the first 2 months, the NSO group received normal saline while the NO and NE groups received nicotine 7 mg/kg, 6 days a week, intraperitoneally. The following 2 months, normal saline and nicotine administration was stopped and was replaced with oral supplementation of olive oil for the NSO and NO groups and oral supplementation of palm vitamin E (60 mg/kg) for the NE group. Both femurs were harvested to determine the gene expression of bone morphogenetic protein-2 (BMP-2), Osterix (OSX), and Runt-related transcription factor 2 (RUNX2). Nicotine significantly downregulated the gene expression. This effect was reversed by palm vitamin E treatment. In conclusion, palm vitamin E may play a role in osteoblast differentiation and can be considered as an anabolic agent to treat nicotine-induced osteoporosis.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit
  6. Hadzir SN, Ibrahim SN, Abdul Wahab RM, Zainol Abidin IZ, Senafi S, Ariffin ZZ, et al.
    Cytotherapy, 2014 May;16(5):674-82.
    PMID: 24176546 DOI: 10.1016/j.jcyt.2013.07.013
    Suspension mononuclear cells (MNCs) can be differentiated into osteoblasts with the induction of ascorbic acid and β-glycerophosphate. The aim of this study was to determine the ability of suspension MNCs to differentiate into osteoblasts using ascorbic acid only.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/genetics
  7. Foo LH, Suzina AH, Azlina A, Kannan TP
    J Biomed Mater Res A, 2008 Oct;87(1):215-21.
    PMID: 18085658
    Coral matrix of Porites sp. has the suitable properties for bone cell growth. This study was aimed to study the gene expression levels of osteoblast specific genetic markers; RUNX2, osteopontin, alkaline phosphatase and osteocalcin from osteoblasts seeded in coral scaffold, which are important in determining the feasibility of osteoblasts. Human osteoblasts were inoculated onto the processed coral in Dulbecco's Minimum Essential Medium. The cells were trypsinized on day 1, 7, 14, 18, and 21 and added with RNALater for preservation of RNA in cells. The RNA was extracted using commercial RNA extraction kit and the respective genes were amplified using RT-PCR kit and analyzed qualitatively on 1.5% agarose gel. The expressions were evaluated with the Integrated Density Value based on the intensity of band for different periods of cell harvest. Increased expressions of the RUNX2, osteopontin, alkaline phosphatase and osteocalcin genes in the present study proved that coral is a favorable carrier for osteogenetically competent cells to attach and remain viable.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/genetics
  8. Ariffin SH, Manogaran T, Abidin IZ, Wahab RM, Senafi S
    Curr Stem Cell Res Ther, 2017;12(3):247-259.
    PMID: 27784228 DOI: 10.2174/1574888X11666161026145149
    Stem cells (SCs) are capable of self-renewal and multilineage differentiation. Human mesenchymal stem cells (MSCs) and haematopoietic stem cells (HSCs) which can be obtained from multiple sources, are suitable for application in regenerative medicine and transplant therapy. The aim of this review is to evaluate the potential of genomic and proteomic profiling analysis to identify the differentiation of MSCs and HSCs towards osteoblast and odontoblast lineages. In vitro differentiation towards both of these lineages can be induced using similar differentiation factors. Gene profiling cannot be utilised to confirm the lineages of these two types of differentiated cells. Differentiated cells of both lineages express most of the same markers. Most researchers have detected the expression of genes such as ALP, OCN, OPN, BMP2 and RUNX2 in osteoblasts and the expression of the DSPP gene in odontoblasts. Based on their cell-type specific protein profiles, various proteins are differentially expressed by osteoblasts and odontoblasts, except for vimentin and heterogeneous nuclear ribonucleoprotein C, which are expressed in both cell types, and LOXL2 protein, which is expressed only in odontoblasts.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/genetics; Core Binding Factor Alpha 1 Subunit/metabolism
  9. Bukhari SNA, Hussain F, Thu HE, Hussain Z
    J Integr Med, 2019 Jan;17(1):38-45.
    PMID: 30139656 DOI: 10.1016/j.joim.2018.08.003
    OBJECTIVE: The present study explored the effects of the combined herbal therapy consisting of curcumin (CUR) and Fructus Ligustri Lucidi (FLL) on aspects of bone regeneration.

    METHODS: Prior to analyzing the ability of this novel combined herbal therapy to promote aspects of bone regeneration, its cytotoxicity was determined using MC3T3-E1 cells (pre-osteoblast model). Cell proliferation was evaluated using phase-contrast microscopy and cell differentiation was estimated using alkaline phosphatase activity. The effect of the combined herbal therapy (CUR + FLL) was also assessed in terms of mineralization in the extracellular matrix (ECM) of cultured cells. Further, to explore the molecular mechanisms of bone formation, time-dependent expression of bone-regulating protein biomarkers was also evaluated.

    RESULTS: Combined herbal therapy (CUR + FLL) significantly upregulated the viability, proliferation and differentiation of MC3T3-E1 cells compared to the monotherapy of CUR or FLL. The magnitude of ECM mineralization (calcium deposition) was also higher in MC3T3-E1 cells treated with combined therapy. The time-dependent expression of bone-forming protein biomarkers revealed that the tendency of expression of these bone-regulating proteins was remarkably higher in cells treated with combined therapy.

    CONCLUSION: The co-administration of CUR and FLL had superior promotion of elements of bone regeneration in cultured cells, thus could be a promising alternative herbal therapy for the management of bone erosive disorders such as osteoporosis.

    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/genetics; Core Binding Factor Alpha 1 Subunit/metabolism
  10. Tan SL, Ahmad RE, Ahmad TS, Merican AM, Abbas AA, Ng WM, et al.
    Cells Tissues Organs (Print), 2012;196(4):325-38.
    PMID: 22653337
    The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been shown to improve tendon repair. It has been hypothesized that further improvements may be achieved when GDF-5 is used to promote cell proliferation and induce tenogenic differentiation in human bone marrow-derived mesenchymal stem cells (hMSCs). However, the optimal conditions required to produce these effects on hMSCs have not been demonstrated in previous studies. A study to determine cell proliferation and tenogenic differentiation in hMSCs exposed to different concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No significant changes were observed in the cell proliferation rate in hMSCs treated at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic differentiation at 100 ng/ml, as reflected by (1) a significant increase in total collagen expression, similar to that of the primary native human tenocyte culture; (2) a significant upregulation in candidate tenogenic marker gene expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type-I collagen to type-III collagen expression was elevated to levels similar to that of human tenocyte cultures, and (4) a significant downregulation of the non-tenogenic marker genes runt-related transcription factor 2 and sex determining region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC differentiation into other lineages. In conclusion, GDF-5 does not alter the proliferation rates of hMSCs, but, instead, induces an optimal tenogenic differentiation response at 100 ng/ml.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/genetics
  11. Isa ZM, Schneider GB, Zaharias R, Seabold D, Stanford CM
    Int J Oral Maxillofac Implants, 2006 Mar-Apr;21(2):203-11.
    PMID: 16634490
    PURPOSE: The objective of this study was to test the hypothesis that fluoride-modified titanium surfaces would enhance osteoblast differentiation. Osteoblast growth on a moderately rough etched fluoride-modified titanium surface (alteration in cellular differentiation) was compared to osteoblast growth on the same surface grit-blasted with titanium dioxide. The potential role of nanometer-level alterations on cell shape and subsequent differentiation was then compared.
    MATERIALS AND METHODS: Human embryonic palatal mesenchymal (HEPM) cultures were incubated on the respective surfaces for 1, 3, and 7 days, followed by analysis for cell proliferation, alkaline phosphatase (ALP) -specific activity, and mRNA steady-state expression for bone-related genes (ALP, type I collagen, osteocalcin, bone sialoprotein [BSP] II, Cbfa1, and osterix) by real-time polymerase chain reaction (PCR).
    RESULTS: The different surfaces did not alter the mRNA expression for ALP, type I collagen, osterix, osteocalcin, or BSP II. However, Cbfa1 expression on the fluoride-modified titanium surface was significantly higher (P < .001) at 1 week. The number of cells on this surface was 20% lower than the number of cells on the surface TiO2-blasted with 25-microm particles but not significantly different from the number of cells on the surface TiO2-blasted with 125-microm particles. Cells grown on all the titanium surfaces expressed similar levels of ALP activity.
    CONCLUSIONS: The results indicated that a fluoride-modified surface topography, in synergy with surface roughness, may have a greater influence on the level of expression of Cbfa1 (a key regulator for osteogenesis) than the unmodified titanium surfaces studied.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/biosynthesis*
  12. Parvaneh M, Karimi G, Jamaluddin R, Ng MH, Zuriati I, Muhammad SI
    Clin Interv Aging, 2018;13:1555-1564.
    PMID: 30214175 DOI: 10.2147/CIA.S169223
    Purpose: Osteoporosis is one of the major health concerns among the elderly population, especially in postmenopausal women. Many menopausal women over 50 years of age lose their bone density and suffer bone fractures. In addition, many mortality and morbidity cases among the elderly are related to hip fracture. This study aims to investigate the effect of Lactobacillus helveticus (L. helveticus) on bone health status among ovariectomized (OVX) bone loss-induced rats.

    Methods: The rats were either OVX or sham OVX (sham), then were randomly assigned into three groups, G1: sham, G2: OVX and G3: OVX+L. helveticus (1 mL of 108-109 colony forming units). The supplementation was force-fed to the rats once a day for 16 weeks while control groups were force-fed with demineralized water.

    Results: L. helveticus upregulated the expression of Runx2 and Bmp2, increased serum osteocalcin, bone volume/total volume and trabecular thickness, and decreased serum C-terminal telopeptide and total porosity percentage. It also altered bone microstructure, as a result increasing bone mineral density and bone strength.

    Conclusion: Our results indicate that L. helveticus attenuates bone remodeling and consequently improves bone health in OVX rats by increasing bone formation along with bone resorption reduction. This study suggests a potential therapeutic effect of L. helveticus (ATCC 27558) on postmenopausal osteoporosis.

    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/metabolism*
  13. Siew Ching H, Thirumulu Ponnuraj K, Luddin N, Ab Rahman I, Nik Abdul Ghani NR
    Polymers (Basel), 2020 Sep 17;12(9).
    PMID: 32957636 DOI: 10.3390/polym12092125
    This study aimed to investigate the effects of nanohydroxyapatite-silica-glass ionomer cement (nanoHA-silica-GIC) on the differentiation of dental pulp stem cells (DPSCs) into odontogenic lineage. DPSCs were cultured in complete Minimum Essential Medium Eagle-Alpha Modification (α-MEM) with or without nanoHA-silica-GIC extract and conventional glass ionomer cement (cGIC) extract. Odontogenic differentiation of DPSCs was evaluated by real-time reverse transcription polymerase chain reaction (rRT-PCR) for odontogenic markers: dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), osteocalcin (OCN), osteopontin (OPN), alkaline phosphatase (ALP), collagen type I (COL1A1), and runt-related transcription factor 2 (RUNX2) on day 1, 7, 10, 14, and 21, which were normalized to the house keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Untreated DPSCs were used as a control throughout the study. The expressions of DSPP and DMP1 were higher on days 7 and 10, that of OCN on day 10, those of OPN and ALP on day 14, and that of RUNX2 on day 1; COL1A1 exhibited a time-dependent increase from day 7 to day 14. Despite the above time-dependent variations, the expressions were comparable at a concentration of 6.25 mg/mL between the nanoHA-silica-GIC and cGIC groups. This offers empirical support that nanoHA-silica-GIC plays a role in the odontogenic differentiation of DPSCs.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit
  14. Berahim Z, Moharamzadeh K, Rawlinson A, Jowett AK
    J. Periodontol., 2011 May;82(5):790-7.
    PMID: 21080786 DOI: 10.1902/jop.2010.100533
    Cell-based therapy using autologous cells has been suggested as a potential approach for periodontal tissue regeneration. Spheroid systems are a form of three-dimensional cell culture that promotes cell matrix interaction, which could recapitulate the aspect of cell homeostasis in vivo. The aim of this study is to assess the interaction of periodontal fibroblast spheroids with synthetic and collagen-based membranes that have been used in guided tissue regeneration.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/analysis
  15. Raghavendran HR, Mohan S, Genasan K, Murali MR, Naveen SV, Talebian S, et al.
    Colloids Surf B Biointerfaces, 2016 Mar 1;139:68-78.
    PMID: 26700235 DOI: 10.1016/j.colsurfb.2015.11.053
    Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering.
    Matched MeSH terms: Core Binding Factor Alpha 1 Subunit/genetics; Core Binding Factor Alpha 1 Subunit/metabolism
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